Drug Shortages: A Headache for Physicians

Physicians are opening medicine cabinets, only to find certain drugs missing.

Increase in demand. Manufacturer shortages. Market withdrawal. Inadequate products. Unavailable raw material.

The Food and Drug Administration cites these reasons for some of the worst shortages in memory of pharmaceutical companies' ability to bring to market prescription drugs that treat life-threatening ailments ranging from cancer to serious blood disorders. As 2012 approaches, it appears the situation will get worse, despite efforts to boost supplies.

According to the White House, while a small number of drugs experience a shortage in any given year, the number of prescription drug shortages in the U.S. has nearly tripled between 2005 and 2010, with the shortages becoming more severe and frequent.

Lawrence A. Solberg Jr., MD, PhD, professor of medicine in the Department of Hematology/Oncology at the Mayo Clinic in Jacksonville, FL, says the drug shortages have been life-threatening to patients with blood-related diseases, particularly those with cancers such as leukemia, lymphoma, and myeloma.

As a result, physicians have had to choose alternative, less effective, and sometimes more toxic therapies for patients when first-line treatments were not available, says Solberg, who is chairman of the American Society of Hematology Committee on Practice. The society represents 16,000 clinicians, practitioners, and scientists who evaluate blood and blood related diseases.

"Imagine sitting there, as a patient with cancer, and your physician says, 'Sorry, We just don't have the drug right now to start your treatment.' It's a huge shock, a horrible anxiety," Solberg told HealthLeadersMedia. "And from a physician's point of view, say you are planning a treatment and have six cycles and go over six months. You may have one of the drugs right now, but how do we know three months down the road if there might be a shortage? You are partway down the treatment course and it affects that treatment course. You may be forced to use a different regimen, and perhaps the outcome in terms of cure is the same, but the toxicity profile differs."

As of August 31, 2011, there were 200 national drug shortages reported, compared to the overall total of 211 in all of 2010, according to Solberg. Some of the drug shortages have lasted for months. He says a six-month shortage of cytarabine, part of a standard therapy for certain leukemias and lymphoma, has been particularly detrimental.

He told the FDA about the case of a 50-year-old man with primary refractory diffuse large B-cell lymphoma who was receiving chemotherapy to prepare him for a bone marrow transplant. The patient received the first part of the chemotherapy and was responding well, Solberg says.

The treatment schedule called for cytarabine to be included in the second dose of chemotherapy, but because it was not available, the "physician was forced to choose an alternative therapy that was more toxic," Solberg said. "The patient was not able to receive the transplant and died from complications."

"This story is one example of several cases that have recently been described to ASH about physicians having to give patients less effective or more toxic alternatives," he told the FDA. "The increasing number of drug shortages has significantly affected the practice of hematology because the standard therapies frequently used include older, sterile injectable products that are particularly vulnerable to production, marketing, and business factors."

Another impact has been on as many as 200 clinical trials that have been interrupted by the shortages, Solberg says.

The drug shortage has become such a hot-button issue that President Barack Obama issued an executive order last month requiring the FDA to take action.

In the weeks after the executive order, a study conducted by the IMS Institute for Healthcare Informatics, a health research company based in Danbury, CT, shed some light on the pattern of drug shortages.

The shortages are primarily limited to generic injectables and a few key disease areas, but troublesome nevertheless, according to Murray Aitken, the institute's executive director.

In a webinar, Aitken noted that 16% of the products in short supply are oncology drugs, which may affect as many as 550,000 patients. Other affected disease areas include infections, cardiovascular disease, central nervous system, and pain. More than 80% of the products are generic and more than 80% are injectables, according to the report.

Over the last five years, White House data indicates that the demand for sterile injectable cancer treatments has increased by about 20%, without a corresponding increase in capacity. The FDA has developed a page on its website giving an overview of current drug shortages. (Healthcare professionals and patients are encouraged to notify the FDA about shortages at drugshortages@fda.hhs.gov.)

According to FDA estimates, about 42% of the 2010 drug shortages were caused by product quality issues. While ensuring safety standards is paramount, the FDA also needs to determine whether its evaluation of product quality is accurate, Solberg says.

The IMS Institute and other healthcare groups, such as the American Society of Hematology, have recommended that the FDA establish an early warning system to improve drug supply monitoring, which is being considered in legislation introduced in Congress. Lawmakers are also considering other plans, such as establishing economic incentives to produce medically necessary drugs in shortage. Some Democratic Senators are calling for hearings on the drug shortages, as well as seeking a General Accountability Office probe.

In the meantime, drug manufacturers say they are working together to examine and adjust their manufacturing schedules for "life-saving" drugs that could be susceptible to shortages.

Still, physicians and patients must be vigilant about drug shortages. Only a few weeks after Solberg was relieved to learn that cytarabine had returned to the market, he received a letter on November 21 from Janssen Products, LP, about delays in the availability of its cancer-fighting drug DOXIL.

"This suspension of manufacturing will impact the production and release of DOXIL, which remains in short supply," the pharmaceutical company wrote. "We are not able to estimate timing when DOXIL may return to market."

Unfortunately, Solberg, says, physicians like him will probably receive more letters like that from other drug manufacturers in the months ahead.